Perioperative Outcomes Following Surgical Resection of Renal Cell Carcinoma with Inferior Vena Cava Thrombus Extending Above the Hepatic Veins: A Contemporary Multicenter Experience

Background

Surgery for renal cell carcinoma (RCC) patients with inferior vena cava (IVC) thrombus above the hepatic veins is technically complex and associated with an increased risk of perioperative morbidity and mortality. However, minimal data exist that describe contemporary perioperative outcomes at major referral centers or the prognostic factors associated with poor outcomes.

Objective

To determine the preoperative predictors of major complications and 90-d mortality after surgery in RCC patients who have IVC thrombus above the hepatic veins.

Design, setting, and participants

We reviewed medical records of all RCC patients who had IVC tumor thrombus above hepatic veins and had had surgery between January 2000 and December 2012 at the Mayo Clinic, M.D. Anderson Cancer Center, University of Texas Southwestern Medical Center, and the University of Wisconsin Hospital.

Outcome measurement and statistical analysis

Major complications recorded were defined as ≥3A according to the Clavien-Dindo system within 90 d of surgery. Univariate and multivariate analyses were used to evaluate associations of preoperative variables with risk of major complications or 90-d mortality.

Results and limitations

A total of 162 patients were identified for study (level 3, 4 in 69, 93 patients, respectively, according to the Neves classification). Cardiopulmonary bypass was used in 60 of 162 patients (37.5%), and 40 patients (24.7%) had preoperative angioembolization. Major complications were reported in 55 patients (34.0%), with the most common being respiratory, cardiac, and hematologic issues. After multivariate analysis, preoperative systemic symptoms and level 4 thrombus were independently associated with increased risk of major complications. Mortality was reported in 17 patients (10.5%) within 90 d after surgery. After multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status (PS) and low serum albumin were preoperative factors independently associated with increased risk of 90-d mortality.

Conclusions

Contemporary perioperative mortality and major complication rates for RCC patients who have upper-level thrombus are 10% and 34%, respectively. Patients who have ECOG PS >1 or low serum albumin have increased risk for perioperative mortality.     

Finger bone immaturity and 2D:4D ratio measurement error in the assessment of the hyperandrogenic hypothesis for the etiology of autism spectrum disorders

Emerging hypotheses suggest a causal role for prenatal androgen exposure in some cases of autism spectrum disorders (ASD). The ratios of the lengths of the bones of the 2nd to the 4th digit (2D:4D) are purported to be markers for prenatal androgen exposure and to be established early in gestation. Elongation of the 4th digit in response to testosterone is said to reduce 2D:4D in males versus females. We examined the ratios of bones from the left hand radiographs of 75 boys and 6 girls 4-8 years of age, diagnosed with ASD, to evaluate digit ratio as a marker for gestational androgen exposure. Contrary to our expectations, girls had reduced 2D:4D compared to boys but the difference was not significant (Cohen's D 0.51-0.66, P > 0.05). The limited sample size for this study and the absence of a referent group precluded providing robust estimates for girls and identifying possible statistical differences between the sexes. Tanner-Whitehouse 3 (TW3) rating of finger bone growth suggested relative immaturity of the 4th relative to the 2nd digits. Positive correlations were detected for 2D:4D ratios, body mass index (r = 0.23, P = 0.039), chronologic age (r = 0.35, P = 0.001), and skeletal age (r = 0.42, P < 0.0001). The TW3 ratings and associations between 2D:4D ratios and indicators of growth suggest that digits develop at different rates. This asynchronous development may produce differences in 2D:4D over time which could lead to erroneous interpretation of androgen exposure in utero among young ASD children.     

美国教学医院教师专业发展的全国性调查

在当前医学教育持续变革的背景中,医学教师的专业发展成为广泛关注的焦点.为了解目前美国以提高教师的教学技能为目标的教师专业发展(faculty development,FD)活动的参与率、课程设计、教学方法和评估策略等情况,美国约翰·霍普金斯大学预防、流行病学和临床研究中心采取邮件调查的方式,对美国277家教学医院进行了调查.     

Survivin and b7-h1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is an immunogenic tumor that can progress in the presence of an intact host immune system. We previously reported that survivin and B7-H1 are independently associated with disease progression and death when expressed by ccRCC tumors. Herein, we examine the clinical effect of ccRCC combined expression of both survivin and B7-H1. EXPERIMENTAL DESIGN: Specimens from 298 patients who underwent nephrectomy for ccRCC between 1990 and 1994 were immunohistochemically stained for survivin and B7-H1. Cancer-specific survival was estimated using the Kaplan-Meier method. Associations of both markers with ccRCC death were assessed using Cox proportional hazards regression models. RESULTS: At last follow-up, 94 patients died from ccRCC. Among the living patients, the median follow-up was 11.2 years (range, 0-15 years). There were 177 (59.4%) survivin(Low)/B7-H1(-), 51 (17.1%) survivin(Hi)/B7-H1(-), 29 (9.7%) survivin(Low)/B7-H1(+), and 41 (13.8%) survivin(Hi)/B7-H1(+) tumors. The 5-year cancer-specific survival rates for patients within each group were 89.3%, 59.7%, 70.0%, and 16.2%, respectively. Combined survivin(Hi)/B7-H1(+) expression was associated with ccRCC death univariately (risk ratio, 12.82; 95% confidence interval, 7.50-21.92; P < 0.001) and in multivariate analysis (risk ratio, 2.81; 95% confidence interval, 1.56-5.04; P < 0.001). Survivin(Hi)/B7-H1(+) tumors exhibited increased levels of infiltrating mononuclear cells and survivin-specific T cells compared with survivin(Low)/B7-H1(-) tumors. CONCLUSION: Patients with survivin(Hi)/B7-H1(+) ccRCC tumors are at increased risk of ccRCC death. Survivin(Hi)/B7-H1(+) tumors also harbor increased amounts of infiltrating mononuclear cells and survivin-specific T cells relative to survivin(Low)/B7-H1(-) tumors. Taken together, dual expression of survivin and B7-H1 can be used to predict ccRCC tumor aggressiveness.     

PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma.

PURPOSE: B7-H1 is expressed by clinically aggressive forms of renal cell carcinoma (RCC) and predicts adverse outcome. B7-H1 is known to impair host immunity via interaction with the Programmed Death-1 (PD-1) receptor, which is expressed by activated T cells. Levels of immune cells expressing PD-1 (PD-1(+)) in clinical RCC tumors have not been evaluated. Thus, we tested whether immune cell PD-1 expression is observed within aggressive RCC tumors. EXPERIMENTAL DESIGN: Between 2000 and 2003, 267 patients underwent nephrectomy at our institution for clear cell RCC and had fresh-frozen tissue available for review. These RCC specimens were immunostained using anti-PD-1 (clone MIH4) and outcome analyses were conducted. RESULTS: Mononuclear immune cell infiltration was observed in 136 (50.9%) specimens. PD-1(+) immune cells were present in 77 of these 136 (56.6%) tumors. In contrast, RCC tumor cells did not express PD-1. Patients with PD-1(+) immune cells were significantly more likely to harbor B7-H1(+) tumor cells (P < 0.001), larger tumors (P = 0.001), and tumors of higher nuclear grade (P = 0.001). Likewise, intratumoral PD-1(+) immune cells were associated with advanced tumor-node-metastasis stage (P = 0.005), coagulative tumor necrosis (P = 0.027), and sarcomatoid differentiation (P = 0.008). With a median follow-up of 2.9 years, 52 patients died from RCC. Univariately, patients with PD-1(+) immune cells were at significant risk of cancer-specific death compared with PD-1(-) patients (risk ratio, 2.24; P = 0.004). CONCLUSIONS: Levels of immune cells expressing PD-1 were increased in patients with high-risk RCC tumors. Interactions between immune cell PD-1 and B7-H1 may promote cancer progression by contributing to immune dysfunction in patients with RCC.     

Comorbidity of axis I and axis II disorders in patients who attempted suicide

OBJECTIVE: The authors compared the characteristics of suicide attempters with and without comorbid psychiatric and personality disorders to identify factors that explain the high suicide risk associated with psychiatric comorbidity. METHOD: A representative group of 111 patients who had attempted suicide (72 female and 39 male) was assessed for psychiatric and personality disorders according to ICD-10 criteria. The characteristics of patients with both types of disorder were compared with those of patients without comorbid disorders. A semistructured interview schedule and standardized questionnaires were used to investigate patients' background characteristics, the circumstances of the suicide attempts, psychological characteristics, and outcome after 12-20 months. RESULTS: Comorbidity of psychiatric and personality disorders was present in 49 patients (44%). More patients with comorbid disorders had made previous suicide attempts (N=41 [84%] versus N=28 [45%]) and repeated attempts during the follow-up period (N=25 [51%] versus N=9 [15%]). Differences in precipitants and motives for the index episode were also found: patients with comorbid disorders were more depressed and hopeless, reported more episodes of aggression, were more impulsive, and had lower self-esteem and poorer problem-solving skills. Differences in self-esteem and problem-solving skills distinguished between the groups in a stepwise discriminant function analysis. More of the patients with comorbid disorders reported not being loved by their parents and parental suicidal behavior. CONCLUSIONS: Suicide attempters with comorbid psychiatric and personality disorders show marked differences from those without both of these disorders. Comorbidity may contribute to greater suicide risk. Some of the characteristics of patients with comorbid disorders pose major clinical challenges that should be addressed in an effort to reduce suicide risk.     

A prototype HeartQuest ventricular assist device for particle image velocimetry measurements

The objective of this study is to fully characterize the flow within the HeartQuest ventricular assist device (VAD), a magnetically levitated centrifugal VAD, using particle image velocimetry (PIV) to identify regions of potential high shear or stagnation and validate and refine computational models of the flow. An acrylic model of the pump was designed and constructed to allow optical access into all interior regions of the pump. The geometry of the exterior housing and the use of a novel working fluid make quantitative measurements of velocity within the exit volute, blade passage, cut-water, blade tip clearance, and pump inlet possible. Highly accurate velocity measurements using particle PIV have been made in one region (the inlet elbow), and measurements in the other critical regions of the pump will be made. These measurements are used for investigation of regions with potential for hemolysis resulting from high shear stress or with potential for thrombosis caused by recirculation or stagnation. Quantitative velocity data are also needed for comparison with computational fluid dynamics (CFD) models of the VAD. In this study, experiments have again proven to be an essential complement to CFD for thorough investigations of the flow inside the pump.     

A randomized controlled trial of continuous positive airway pressure in mild obstructive sleep apnea

A common clinical dilemma faced by sleep physicians is in deciding the level of severity at which patients with obstructive sleep apnea (OSA) should be treated. There is particular uncertainty about the need for, and the effectiveness of, treatment in mild cases. To help define the role of nasal continuous positive airway pressure (CPAP) treatment in mild OSA we undertook a randomized controlled cross-over trial of CPAP in patients with an apnea- hypopnea index (AHI) of 5 - 30 (mean, 12.9 +/- 6.3 SD). Twenty-four-hour blood pressure and neurobehavioral function were measured at baseline, after 8 wk of treatment with CPAP, and after 8 wk of treatment with an oral placebo tablet. Twenty-eight of 42 patients enrolled in the study completed both treatment arms. Baseline characteristics were not different between those who completed the study and those who did not complete the study. Patients used CPAP for a mean (SD) of 3.53 (2.13) h per night and the mean AHI on the night of CPAP implementation was 4.24 (2.9). Nasal CPAP improved self-reported symptoms of OSA, including snoring, restless sleep, daytime sleepiness, and irritability (in-house questionnaire), more than did placebo, but did not improve objective (Multiple Sleep Latency Test) or subjective (Epworth Sleepiness Scale) measures of daytime sleepiness. We found no benefit of CPAP over placebo in any tests of neurobehavioral function, generic SF-36 (36-item Short Form Medical Outcomes Survey) or sleep-specific (Functional Outcomes of Sleep Questionnaire) quality of life questionnaires, mood score (Profile of Moods States and Beck Depression Index), or 24-h blood pressure. However, the placebo tablet resulted in a significant improvement in a wide range of functional variables compared with baseline. This placebo effect may account for some of the treatment responses to CPAP observed previously in patients with mild OSA.